Plasma markers of B-cell activation and clonality in pediatric liver and hematopoietic stem cell transplant recipients

Eric A. Engels, Barbara Savoldo, Ruth M. Pfeiffer, Rene Costello, Adriana Zingone, Helen E. Heslop, Ola Landgren

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background: Transplant recipients are at risk of posttransplant lymphoproliferative disease (PTLD). Methods: Thirty-six pediatric transplant recipients were evaluated (18 hematopoietic stem cell and 18 liver recipients; 12 had PTLD). We studied 207 longitudinal plasma samples from these recipients for three markers of B-cell activation or clonality: immunoglobulin free light chains (FLCs), soluble CD30 (sCD30), and monoclonal immunoglobulins (M-proteins). Results: Kappa FLCs, lambda FLCs, and sCD30 were elevated in 20.8%, 28.0%, and 94.2% of plasma specimens, respectively. Free light chain and sCD30 levels increased significantly 1.18 to 1.82 fold per log10 Epstein-Barr virus (EBV) load in peripheral blood. Five PTLD cases manifested elevated FLCs with an abnormal kappa/lambda ratio, suggesting monoclonal FLC production. M-proteins were present in 91% of PTLD cases versus 50% to 67% of other recipients with high or low EBV loads (P=0.13). Concordance of FLCs, M-proteins, and PTLD tumor light chain restriction was imperfect. For example, one PTLD case with an IgG lambda M-protein had a tumor that was kappa restricted, and another case with an M-protein had a T-cell PTLD. In an additional case, an IgM kappa M-protein and excess kappa FLCs were both detected in plasma at PTLD diagnosis; although the tumor was not restricted at diagnosis, kappa restriction was present 5 years later when the PTLD relapsed. Conclusions: Plasma markers of B-cell dysfunction are frequent after transplantation and associated with poor EBV control. These abnormal markers may be produced by oligoclonal B-cell populations or PTLD tumor cells and could potentially help identify recipients at high risk of PTLD.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalTransplantation
Volume95
Issue number3
DOIs
StatePublished - Feb 15 2013

Keywords

  • B cell
  • Cytokines
  • Epstein-Barr virus
  • Immune monitoring
  • Immunoglobulins
  • Posttransplant lymphoproliferative disease

ASJC Scopus subject areas

  • Transplantation

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